The long-term goal of this study is to understand the mechanism of motor neuron diseases. The specific aims of this proposal are to test whether or not survival of motor neurons is controlled by the peripheral target of innervation or by the afferent input to the motor neuron. The role of the target in the control of survivors will be determined by reducing the size of the target for the trochlear motor neurons. For this, the superior oblique muscle of quail embryos will be grafted in the place of that of duck embryos. The development of the target, motor neurons and neuromuscular connections will be examined morphologically and physiologically. The number of trochlear motor neurons surviving by virtue of innervating the smaller target will be counted. The role of afferent input in the control of neuron numbers will be determined by monitoring neuron survival in the absence of afferent input and also following increased afferents. The troclear motor neurons will be deprived of their afferent input by removal of the hindbrain. The amount of afferent projection will be increased by substituting the hindbrain of quail embryos with the same neural tissue from duck embryos. Results of the proposed study should indicate whether the mechanism for the control of motor neuron numbers resides in the target muscle or in the CNS.